Association of flame retardants, polybrominated diethyl ethers (PBDEs), with vitamin D in female subjects

Introduction: A class of flame retardants, polybrominated diethyl ethers (PBDEs), are known endocrine disrupters and may induce the hepatic enzymes CYP24 and CYP3A that promote 25-hydroxylation of vitamin D₃. Therefore, this study examined the association of PBDEs with vitamin D₃ (25(OH)D₃) and the active 1,25-dihydrovitamin D₃ (1,25(OH)₂D₃) in a cohort of non-obese women.

Methods: 58 female participants (age:31.9 ± 4.6 years; body mass index (BMI):25.7 ± 3.7 kg/m²) had seven indicator PBDEs [PBDE28; PBDE47; PBDE99; PBDE100; PBDE153; PBDE154; PBDE183] measured using high resolution gas chromatography, with ƩPBDE level calculated. 25(OH)D₃ and 1,25(OH)₂D₃ levels were determined by isotope-dilution liquid chromatography tandem mass spectrometry. Plasma level of calcium/calmodulin-dependent protein kinase type 1 (CaMK1) was measured by Somascan proteomics.

Results: In this cohort, vitamin D₃ (25(OH)D₃) and 1,25(OH)₂D₃ levels were 22.9 ± 11.2 ng/mL and 0.05 ± 0.02 ng/mL, respectively. Of those, 28 had vitamin D deficiency [25(OH)D₃ level <20 ng/mL (<50 nmol/L)]. For the whole group, individual PBDEs (PBDE28; PBDE47; PBDE99; PBDE100; PBDE153; PBDE154; PBDE183) and ƩPBDEs did not correlate with 25(OH)D₃ or its active metabolite 1,25(OH)₂D₃ nor with BMI. For the subset who were 25(OH)D₃ sufficient, negative correlations were found for 1,25(OH)₂D₃ with PBDE153 (ρ = -0.77; p = 0.02) and PBDE100 (ρ = -0.72; p = 0.005). In the subset of women who were 25(OH)D₃ deficient, positive correlations were found for 1,25(OH)₂D₃ with PBDE153 (ρ = 0.68; p = 0.02) and ƩPBDEs (ρ = 0.57; p = 0.03). Using sufficient and deficient subset categories, no correlations were seen with 25(OH)D₃ nor any of the PBDEs, and PBDEs did not correlate to renal function (estimated glomerular filtration rate, eGFR). 1,25(OH)₂D₃ was negatively associated with CaMK1 (r = -0.36; p = 0.03) as was PBDE153 (r = -0.31; p = 0.02).

Conclusion: PBDEs were not associated with 25(OH)D₃, but PBDE100 and 153 correlated with its active 1,25(OH)₂D₃ metabolite and PBDE153 correlated to the calcium modulator CaMKI, suggesting that PBDE effects could either be mediated through vitamin D status or that functional inactivation or inhibition of 1,25(OH)₂D₃ may contribute to the impact of vitamin D deficiency.